Stem cells, quiescence and rectal carcinoma: An unexplored relationship and potential therapeutic target

British Journal of Cancer

Volumn 105, Issue 9, 2011, Pages 1253-1259

  Buczacki, S ^a   Davies, R J ^b   Winton, D J ^a  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^b ADDENBROOKE S HOSPITAL   (United Kingdom)

Author keywords

cancer stem cell; colorectal cancer; intestine; quiescence; stem cell

Indexed keywords

ACTIVATED LEUKOCYTE CELL ADHESION MOLECULE; ANTINEOPLASTIC AGENT; BMI1 PROTEIN; CD133 ANTIGEN; CD24 ANTIGEN; CELL MARKER; HERMES ANTIGEN; INTEGRIN; TUMOR MARKER;

CANCER ADJUVANT THERAPY; CANCER CHEMOTHERAPY; CANCER RESISTANCE; CANCER STEM CELL; CANCER SURGERY; CARCINOGENESIS; CELL CYCLE; CELL DIFFERENTIATION; CELL POPULATION; CELL PROLIFERATION; CELL RENEWAL; CLONOGENESIS; HUMAN; INTESTINE CRYPT; NONHUMAN; PREOPERATIVE RADIOTHERAPY; PRIORITY JOURNAL; RECTUM CARCINOMA; REVIEW; STEM CELL; STEM CELL NICHE; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

CELL CYCLE CHECKPOINTS; COLORECTAL NEOPLASMS; HUMANS; INTESTINES; NEOPLASTIC STEM CELLS; RECTAL NEOPLASMS; STEM CELLS;

EID: 80054974211     PISSN: 00070920     EISSN: 15321827     Source Type: Journal    
DOI: 10.1038/bjc.2011.362     Document Type: Review

References (86)

1. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100: 3983-3988 (Pubitemid 36418143)
2. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457: 608-611
3. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449: 1003-1007 (Pubitemid 350014593)
4. Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3: 730-737 (Pubitemid 27298715)
5. Bruggeman SW, Hulsman D, Tanger E, Buckle T, Blom M, Zevenhoven J, van Tellingen O, van Lohuizen M (2007) Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma. Cancer Cell 12: 328-341 (Pubitemid 47539307)
6. Chaffer CL, Brueckmann I, Scheel C, Kaestli AJ, Wiggins PA, Rodrigues LO, Brooks M, Reinhardt F, Su Y, Polyak K, Arendt LM, Kuperwasser C, Bierie B, Weinberg RA (2011) Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci USA 108: 7950-7955
7. Cheng T, Rodrigues N, Shen H, Yang Y, Dombkowski D, Sykes M, Scadden DT (2000) Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287: 1804-1808
8. Chiba T, Miyagi S, Saraya A, Aoki R, Seki A, Morita Y, Yonemitsu Y, Yokosuka O, Taniguchi H, Nakauchi H, Iwama A (2008) The polycomb gene product BMI1 contributes to the maintenance of tumor-initiating side population cells in hepatocellular carcinoma. Cancer Res 68: 7742-7749
9. Choi D, Lee HW, Hur KY, Kim JJ, Park GS, Jang SH, Song YS, Jang KS, Paik SS (2009) Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma. World J Gastroenterol 15: 2258-2264
10. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005) Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 65: 10946-10951 (Pubitemid 41713363)
11. Cotsarelis G, Sun TT, Lavker RM (1990) Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61: 1329-1337
12. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF (2007) Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA 104: 10158-10163 (Pubitemid 47175279)
13. Dembinski JL, Krauss S (2009) Characterization and functional analysis of a slow cycling stem cell-like subpopulation in pancreas adenocarcinoma. Clin Exp Metastasis 26: 611-623
14. Demidov ON, Timofeev O, Lwin HN, Kek C, Appella E, Bulavin DV (2007) Wip1 phosphatase regulates p53-dependent apoptosis of stem cells and tumorigenesis in the mouse intestine. Cell Stem Cell 1: 180-190 (Pubitemid 47215589)
15. Elrick LJ, Jorgensen HG, Mountford JC, Holyoake TL (2005) Punish the parent not the progeny. Blood 105: 1862-1866 (Pubitemid 40731765)
16. Escobar M, Nicolas P, Sangar F, Laurent-Chabalier S, Clair P, Joubert D, Jay P, Legraverend C (2011) Intestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation. Nat Commun 2: 258
17. Ferrandina G, Martinelli E, Petrillo M, Prisco MG, Zannoni G, Sioletic S, Scambia G (2009) CD133 antigen expression in ovarian cancer. BMC Cancer 9: 221
18. Fujimoto K, Beauchamp RD, Whitehead RH (2002) Identification and isolation of candidate human colonic clonogenic cells based on cell surface integrin expression. Gastroenterology 123: 1941-1948 (Pubitemid 35408318)
19. Furth J KM (1937) The transmission of leukaemia of mice with a single cell. Am J Cancer 31: 276-282
20. Gao MQ, Choi YP, Kang S, Youn JH, Cho NH (2010) CD24+ cells from hierarchically organized ovarian cancer are enriched in cancer stem cells. Oncogene 29: 2672-2680
21. Garcia MI, Ghiani M, Lefort A, Libert F, Strollo S, Vassart G (2009) LGR5 deficiency deregulates Wnt signaling and leads to precocious Paneth cell differentiation in the fetal intestine. Dev Biol 331: 58-67
22. Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1: 555-567 (Pubitemid 350056407)
23. Gracz AD, Ramalingam S, Magness ST (2010) Sox9 expression marks a subset of CD24-expressing small intestine epithelial stem cells that form organoids in vitro. Am J Physiol Gastrointest Liver Physiol 298: G590-G600
24. Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, Scheller J, Rose-John S, Cheroutre H, Eckmann L, Karin M (2009) IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15: 103-113
25. He XC, Zhang J, Tong WG, Tawfik O, Ross J, Scoville DH, Tian Q, Zeng X, He X, Wiedemann LM, Mishina Y, Li L (2004) BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 36: 1117-1121 (Pubitemid 41184475)
26. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1: 313-323 (Pubitemid 47355323)
27. Hermitte F, Brunet de la Grange P, Belloc F, Praloran V, Ivanovic Z (2006) Very low O2 concentration (0.1%) favors G0 return of dividing CD34+ cells. Stem Cells 24: 65-73
28. Honeth G, Bendahl PO, Ringner M, Saal LH, Gruvberger-Saal SK, Lovgren K, Grabau D, Ferno M, Borg A, Hegardt C (2008) The CD44+/CD24-phenotype is enriched in basal-like breast tumors. Breast Cancer Res 10: R53
29. Horsley V, Aliprantis AO, Polak L, Glimcher LH, Fuchs E (2008) NFATc1 balances quiescence and proliferation of skin stem cells. Cell 132: 299-310 (Pubitemid 351172432)
30. Hou NY, Yang K, Chen T, Chen XZ, Zhang B, Mo XM, Hu JK (2010) CD133(+)CD44 (+) subgroups may be human small intestinal stem cells. Mol Biol Rep 38(2): 997-1004
31. Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS, Boman BM (2009) Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res 69: 3382-3389
32. Jaks V, Barker N, Kasper M, van Es JH, Snippert HJ, Clevers H, Toftgard R (2008) Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet 40: 1291-1299
33. Jensen KB, Watt FM (2006) Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence. Proc Natl Acad Sci USA 103: 11958-11963 (Pubitemid 44215793)
34. Kryczek I, Liu S, Roh M, Vatan L, Szeliga W, Wei S, Banerjee M, Mao Y, Kotarski J, Wicha MS, Liu R, Zou W (2011) Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells. Int J Cancer; e-pub ahead of print 8 April 2011
35. Levin TG, Powell AE, Davies PS, Silk AD, Dismuke AD, Anderson EC, Swain JR, Wong MH (2010) Characterization of the intestinal cancer stem cell marker, CD166/ALCAM, in the human and mouse gastrointestinal tract. Gastroenterology 139: 2072-2082
36. Li L, Clevers H (2010) Coexistence of quiescent and active adult stem cells in mammals. Science 327: 542-545
37. Liang D, Shi Y (2011) Aldehyde dehydrogenase-1 is a specific marker for stem cells in human lung adenocarcinoma. Med Oncol; e-pub ahead of print 12 April 2011
38. Liu AY, True LD, LaTray L, Nelson PS, Ellis WJ, Vessella RL, Lange PH, Hood L, van den Engh G (1997) Cell-cell interaction in prostate gene regulation and cytodifferentiation. Proc Natl Acad Sci USA 94: 10705-10710 (Pubitemid 27430798)
39. Lopez-Garcia C, Klein AM, Simons BD, Winton DJ (2010) Intestinal stem cell replacement follows a pattern of neutral drift. Science 330: 822-825
40. Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, Carafa V, Spagnoli G, Terracciano L, Zlobec I (2010) Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer 103: 382-390
41. Lukacs RU, Memarzadeh S, Wu H, Witte ON (2010) Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation. Cell Stem Cell 7: 682-693
42. Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small Jr W, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11: 835-844
43. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133: 704-715 (Pubitemid 351636299)
44. May R, Sureban SM, Hoang N, Riehl TE, Lightfoot SA, Ramanujam R, Wyche JH, Anant S, Houchen CW (2009) Doublecortin and CaM kinase-like-1 and leucine-rich-repeat-containing G-protein-coupled receptor mark quiescent and cycling intestinal stem cells, respectively. Stem Cells 27: 2571-2579
45. McQualter JL, Yuen K, Williams B, Bertoncello I (2010) Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung. Proc Natl Acad Sci USA 107: 1414-1419
46. Merlos-Suarez A, Barriga FM, Jung P, Iglesias M, Cespedes MV, Rossell D, Sevillano M, Hernando-Momblona X, da Silva-Diz V, Munoz P, Clevers H, Sancho E, Mangues R, Batlle E (2011) The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell 8: 511-524
47. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425: 962-967 (Pubitemid 37376927)
48. Montgomery RK, Carlone DL, Richmond CA, Farilla L, Kranendonk ME, Henderson DE, Baffour-Awuah NY, Ambruzs DM, Fogli LK, Algra S, Breault DT (2011) Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc Natl Acad Sci USA 108: 179-184
49. Nishikawa S, Osawa M (2007) Generating quiescent stem cells. Pigment Cell Res 20: 263-270 (Pubitemid 47057316)
50. O'Brien CA, Pollett A, Gallinger S, Dick JE (2007) A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature 445: 106-110 (Pubitemid 46067310)
51. Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25: 1696-1708
52. Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP (2010) Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140: 62-73
53. Potten CS, Booth C, Tudor GL, Booth D, Brady G, Hurley P, Ashton G, Clarke R, Sakakibara S, Okano H (2003) Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation 71: 28-41 (Pubitemid 38230417)
54. Pruszak J, Ludwig W, Blak A, Alavian K, Isacson O (2009) CD15, CD24, and CD29 define a surface biomarker code for neural lineage differentiation of stem cells. Stem Cells 27: 2928-2940
55. Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ (2008) Efficient tumour formation by single human melanoma cells. Nature 456: 593-598
56. Rajasekhar VK, Studer L, Gerald W, Socci ND, Scher HI (2011) Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-kappaB signalling. Nat Commun 2: 162
57. Reya T, Clevers H (2005) Wnt signalling in stem cells and cancer. Nature 434: 843-850 (Pubitemid 40558990)
58. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445: 111-115 (Pubitemid 46067311)
59. Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT (2004) CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 117: 3539-3545 (Pubitemid 39206394)
60. Rodel C, Grabenbauer GG, Papadopoulos T, Bigalke M, Gunther K, Schick C, Peters A, Sauer R, Rodel F (2002) Apoptosis as a cellular predictor for histopathologic response to neoadjuvant radiochemother-apy in patients with rectal cancer. Int J Radiat Oncol Biol Phys 52: 294-303 (Pubitemid 34172996)
61. Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, Basu D, Gimotty P, Vogt T, Herlyn M (2010) A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell 141: 583-594
62. Sangiorgi E, Capecchi MR (2008) Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet 40: 915-920 (Pubitemid 351913652)
63. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469(7330): 415-418
64. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459: 262-265
65. Schepers AG, Vries R, van den Born M, van de Wetering M, Clevers H (2011) Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes. EMBO J 30: 1104-1109
66. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439: 84-88 (Pubitemid 43053633)
67. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432: 396-401 (Pubitemid 39551674)
68. Snippert HJ, van Es JH, van den Born M, Begthel H, Stange DE, Barker N, Clevers H (2009) Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine. Gastroenterology 136: 2187-2194. e1
69. Spitzner M, Emons G, Kramer F, Gaedcke J, Rave-Frank M, Scharf JG, Burfeind P, Becker H, Beissbarth T, Ghadimi BM, Ried T, Grade M (2010) A gene expression signature for chemoradiosensitivity of colorectal cancer cells. Int J Radiat Oncol Biol Phys 78: 1184-1192
70. Sunter JP, Appleton DR, De Rodriguez MS, Wright NA, Watson AJ (1979) A comparison of cell proliferation at different sites within the large bowel of the mouse. J Anat 129: 833-842 (Pubitemid 10164103)
71. Terskikh AV, Easterday MC, Li L, Hood L, Kornblum HI, Geschwind DH, Weissman IL (2001) From hematopoiesis to neuropoiesis: evidence of overlapping genetic programs. Proc Natl Acad Sci USA 98: 7934-7939 (Pubitemid 32642665)
72. Toiyama Y, Inoue Y, Saigusa S, Okugawa Y, Yokoe T, Tanaka K, Miki C, Kusunoki M (2010) Gene expression profiles of epidermal growth factor receptor, vascular endothelial growth factor and hypoxia-inducible factor-1 with special reference to local responsiveness to neoadjuvant chemoradiotherapy and disease recurrence after rectal cancer surgery. Clin Oncol (R Coll Radiol) 22: 272-280
73. van der Flier LG, Haegebarth A, Stange DE, van de Wetering M, Clevers H (2009) OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 137: 15-17
74. Vassilopoulos A, Wang RH, Petrovas C, Ambrozak D, Koup R, Deng CX (2008) Identification and characterization of cancer initiating cells from BRCA1 related mammary tumors using markers for normal mammary stem cells. Int J Biol Sci 4: 133-142 (Pubitemid 351872048)
75. Vermeulen L, De Sousa EMF, van der Heijden M, Cameron K, de Jong JH, Borovski T, Tuynman JB, Todaro M, Merz C, Rodermond H, Sprick MR, Kemper K, Richel DJ, Stassi G, Medema JP (2010) Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol 12: 468-476
76. Vermeulen L, Todaro M, de Sousa Mello F, Sprick MR, Kemper K, Perez Alea M, Richel DJ, Stassi G, Medema JP (2008) Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA 105: 13427-13432
77. Vlashi E, McBride WH, Pajonk F (2009) Radiation responses of cancer stem cells. J Cell Biochem 108: 339-342
78. von Furstenberg RJ, Gulati AS, Baxi A, Doherty JM, Stappenbeck TS, Gracz AD, Magness ST, Henning SJ (2011) Sorting mouse jejunal epithelial cells with CD24 yields a population with characteristics of intestinal stem cells. Am J Physiol Gastrointest Liver Physiol 300: G409-G417
79. Wang X, Hu J, Zhao D, Wang G, Tan L, Du L, Yang J, Hou L, Zhang H, Yu Y, Deng H, Ding M (2005) NestinnegCD24low/-population from fetal Nestin-EGFP transgenic mice enriches the pancreatic endocrine progenitor cells. Pancreas 31: 385-391 (Pubitemid 41566890)
80. Wright MH, Calcagno AM, Salcido CD, Carlson MD, Ambudkar SV, Varticovski L (2008) Brca1 breast tumors contain distinct CD44+/CD24-and CD133+ cells with cancer stem cell characteristics. Breast Cancer Res 10: R10
81. Yao J, Cai HH, Wei JS, An Y, Ji ZL, Lu ZP, Wu JL, Chen P, Jiang KR, Dai CC, Qian ZY, Xu ZK, Miao Y (2010) Side population in the pancreatic cancer cell lines SW1990 and CFPAC-1 is enriched with cancer stem-like cells. Oncol Rep 23: 1375-1382
82. Yeung TM, Gandhi SC, Bodmer WF (2011) Hypoxia and lineage specification of cell line-derived colorectal cancer stem cells. Proc Natl Acad Sci USA 108: 4382-4387
83. Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF (2010) Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci USA 107: 3722-3727
84. Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP (2001) The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med 7: 1028-1034 (Pubitemid 32937383)
85. Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, Poppleton H, Zakharenko S, Ellison DW, Gilbertson RJ (2009) Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 457: 603-607
86. Zhu Z, Hao X, Yan M, Yao M, Ge C, Gu J, Li J (2010) Cancer stem/progenitor cells are highly enriched in CD133+CD44+ population in hepatocellular carcinoma. Int J Cancer 126: 2067-2078